Friday, 3 April 2009

Everything you wanted to know about Chromosome 2 and evolution but were afraid to ask.

I recently joined Yahoo! Answers to give me something to do on my lunch breaks at work by answering peoples' questions about molecular biology and genetics (a niche that needed filling because it only took me a week to become a "Top Contributor" in biology). Yesterday, there was a challenge put towards "evolutionists" (ugh, how I hate that term): give the one (1) piece of evidence you would put forth to a creationist to try and sway his/her opinion on whether humans descended from earlier primates. There is literally a whole boatload of evidence to support man's descent from earlier primates, but picking the single piece of evidence to sway a creationist's opinion was tough. I thought about it for a minute and decided to present the case from Chromosome 2. I thought I'd reproduce my answer here:

You want one convincing proof? Consider this:

I'm sure you've heard that humans and chimpanzees have the vast majority of our DNA in common. You're also probably not convinced by this argument ("I don't understand...so what if two organisms share the same genes? How does this prove that they came from the same lineage?"). But for now, forget about how very similar we are in our genetic sequence and let's focus on our chromosomes.

If you need a refresher, remember that the number of chromosomes a species has tends to stay the same from generation to generation. A fruit fly has four autosomal chromosomes and one pair of sex chromosomes; it's offspring will all have the same number. What about us humans? We have 23 pairs of chromosomes; 46 chromosomes in total. If you took a karyotype - that's a display of all the chromosomes in a cell - of an ape (I know you're skeptical of humans being primates, but lets call 'em primates for now) you'll notice something different from human chromosomes: there's two extra! Apes have 48 chromosomes.

You might wonder how this proves we evolved from an ancestral primate. You might even suspect that it is evidence against such a claim, since an ancestral primate would have had 48 chromosomes, and that number would have likely stayed constant down the generations, while in us, it's different. Well, this information alone does not prove much. But let's take a look at what the genome sequence shows us.

The sequence of the human genome showed an interesting fact about our Chromosome 2. The area around the very centre of chromosome 2 (known as a centromere) looked an awful lot like telomeric DNA. Telomeres are the regions at the very ends of chromosomes; what were they doing in the centre of chromosome 2? Furthermore, each arm of Chromosome 2 had what appeared to be their own centromeres. Chromosome 2 was looking to be quite an oddity. No other human chromosome displayed these characteristics.

Once the chimpanzee genome was sequenced, things got even more interesting. One of the chimpanzee's chromosomes was pretty much identical to the top half of the human Chromosome 2. Another chimpanzee chromosome was nearly identical to the bottom half of Chromosome 2. On top of this, the banding pattern of these two chromosomes (as well as the same chromosomes in many other species of primates) was a complete match to the banding pattern of Chromosome 2.

Coincidence? Not likely. What this is, is evidence of a chromosomal fusion. An ancestral primate, ancestor to humans, chimpanzees and apes, had 24 pairs of chromosomes. Eventually, this lineage diverged: apes and chimps went one way and we humans evolved along a separate path. But something interesting happened in the lineage that was to become humans: the two extra chromosomes from that ancestor fused together end to end to become human Chromosome 2. This is why our Chromosome 2 has what appears to be telomeres in its centre, and what appears to be two extra centromeres, one on each arm.

The only way to explain Chromosome 2's odd characteristics and similarity to other primates is with a chromosomal fusion. And the only way this could be possible is if we were descended from a common primate ancestor.

So, I put the question to you: if you could give only one single line of evidence for man's primate ancestry to change a creationist's mind, what would it be?

That seems a bit convoluted, doesn't it? Let's assume that there is an all powerful creator, whose goal it is to populate the Earth with a diverse number of organisms. Let us posit that there was an "intelligent designer".

One aspect that is behind any good design is efficency. A good design is simple, and not needlessly complex. It does the specified job in the easist manner possible. If an intelligent designer created both humans and our simian siblings, then he did a really poor job at designing us. Would it not have been an "intelligent design" to simply create humans with their own chromosomes and other primates with their own, different, set? Or just make them all the same? Why would an intelligent designer make MOST of them the same but pick one out of the human set and turn it into a sort of patchwork of two primate chromosomes? If it were a design, then it's a pretty poor design; it is not what you would expect from an intelligent designer.

It is, however, something you would expect from the slow, gradual process of evolution. Evolution is not about sleek design. It goes with whatever works, no matter how complex and convoluted the system becomes.

In short: the way in which the human Chromosome 2 compares to the chromosomes in apes and chimps does not bear any hallmark of design; quite to the contrary, if one assumes it IS designed, then it is quite obviously a BAD one. The similarities are not only explained by evolution but also expected given the way evolution works. Furthermore, evolution explains it in a purely naturalistic manner, and does not need to hypothesize the existance of some supernatural entity of which there is no evidence for...you might as well claim that the chromosomes are the way they are due to the action of invisible pink unicorns.

That's a pretty silly position to take, isn't it? Believing "just for the sake of believing" would suggest that there is no rational reason to believe in the first place, so why bother? Are you implying that humans have a need to believe in SOMETHING, so why not believe in God? In that case, why not belive in something tangible, like beliving that humans are intrinsically good and altruistic, or beliving that humanity can make a positive change on our planet? If you want to believe in something just for the sake of believing, then you'd be better off chosing a belief that doesn't involve an invisible misogynistic, petty, jealous, genocidal, tyrannical sky-fairy from an ancient book.

I don't-believe in god just for the sake of it, how about that twist on things? :) Okay I don't really, I have reasons for disbelief now, but there was a time when I decided to break from believing in a god just to see how that went. And things gradually built into it making more and more sense. Like postulating a theory and trying on new lenses to test it. There being no god just seemed to fit better.

Anyway my big post reason was wondering if the chance of that chromosome fusion happening, and being totally unrelated to our having a common lineage, could be calculated?

Any math nerds able to figure this out?

(My dream is to one day take things like this to get an actual number for the probability that evolution didn't occur, ie instead of just saying "really really really unlikely it didn't happen" saying only a 1/1,877,893,749 chance...)

The thing about probabilities, though, is that they don't really tell us much after the fact. You can calculate the odds of winning the lottery as 1 in a billion, say, but that doesn't mean it can't or doesn't happen. Improbability does not equate impossibility.

Many creationists have tried to calculate the probability of biological evolution, but they have all failed, for a few reasons. They often do not understand the math involved and make plenty of mathematical erros; often their lack of understanding of how probabilities work leads to this. They often do not understand the biological processes involved, and make wild, arbitrary estimates for many variables in the calculation. And they almost university rely on the fallacy of large numbers": they throw out such large (or such small) numbers that the average person's mind cannot adequately comprehend the size of those numbers, and then people will tend to accept their argument simply because it is beyond their comprehension. Take any probability in regards to evolution not occuring with a grain of salt!

Interesting article you wrote, but there are a few points that I would like to mention (and forgive me if these were addressed in the comments section; I didn't have time to read through all the comments).

It is my understanding that you do not doubt that human chromosome 2 is the result of a chromosomal fusion; but you do not accept that such a fusion is indicative of common descent. You make the claim that there is "to date no conclusive evidence that this fusion is indeed the fusion of 2 "ape" chromosomes and not just the fusion of two human chromosomes". Furthermore, you say "The evidence in support of the ape chromosome fusion lies almost exclusively in the banding pattern sequence which is remarkably similar". I would disagree with this; while the similarities in banding patterns between human Chromosome 2 and the two ape chromosomes are incredibly similar, this similarity does not exclusively compose the majority of the evidence for a fusion event in an ape ancestor. The banding patterns supply evidence, but the real evidence lies in a technique called fluorescent in situ hybridization (or FISH). FISH allows one to make probes that are specific to individual chromosomes and "paint" each chromosome (or particular parts of chromosomes) a unique colour. These probes are VERY specific, so if you make a probe for the centromere of chromosome 2 that fluoresces red, then the centromere of chromosome 2 and ONLY that centromere will always fluoresce red. Interestingly enough, such a probe also hybridizes to the telomeres of two different chromosomes in chimpanzees and cynomolgus monkies (1). This means that the human centromeres and primate telomeres dont simply look the same (as suggested by the banding pattern) but for all intents and purposes ARE the same right down to the sequence (as suggested by the FISH results). You point out that the banding pattern of different chromosomes look similar anyway, but using FISH gets past this problem, since the probes are specific.

There are only two possible explanations for this: either humans shared an ancestor with the other primates and experienced a chromosomal fusion, or that they were "designed" that way. My response to Rhology above pointed out the problems with thinking Chromosome 2 was designed in its present form. On top of this, there is no emperical evidence to support the idea of design. You admit this yourself in your article. Luckily for those of us in the "common descent" camp that there is a wide variety of evidence that supports common descent outside of chromosome 2, that it makes the common descent explaination all the more likely.

As an aside, I find it funny how Miller is claiming that a chromosomal fusion would "disprove" common descent - my understanding was that Ken Miller is an ardent supporter of evolution and had no problems accepting common descent from primate ancestors. Perhaps my impressions of him have been incorrect.

As an aside, I find it funny how Miller is claiming that a chromosomal fusion would "disprove" common descent - my understanding was that Ken Miller is an ardent supporter of evolution and had no problems accepting common descent from primate ancestors. Perhaps my impressions of him have been incorrect.

I don't know where you got this. Ken does indeed support the idea of common descent.

I think you're referring to his stance that if there was no fusion, that would tend to disprove common descent.

I'll comment on your FISH response soon. You may also notice the considerable DIFFERENCES in the fusion region which I outlined in the graphics which accompanied my article.

Prehaps I misunderstood what you wrote, then. You say in your article "Dr. Miller states in his talks that this chromosomal difference is unique in that it has the ability to "disprove" evolutionary theory" and "Miller postulates that the total loss of the "missing" pair of chromosomes would "be fatal" and so, there must be another explanation for this difference if common ancestry is true". The way you have it written sounds like Miller is claiming that such a chromosomal fusion would be fatal, and if it really happened, it would disprove common descent.

Well, we could go back and forth I guess about how you're reading it. However, in context with the rest of the article, it's rather plain.

(I've responded below in parenthesis)

Prehaps I misunderstood what you wrote, then. You say in your article "Dr. Miller states in his talks that this chromosomal difference is unique in that it has the ability to "disprove" evolutionary theory" (in other words homo sapiens having 1 less chromosomal pair must be accounted for) and "Miller postulates that the total loss of the "missing" pair of chromosomes would "be fatal" (so simply having 1 less chromosome, (or missing 1) is not an option, i.e., common descent) and so, there must be another explanation for this difference if common ancestry is true". The way you have it written sounds like Miller is claiming that such a chromosomal fusion would be fatal, and if it really happened, it would disprove common descent. (Quite the contrary, i.e., no fusion, no common descent)

I've done quite a bit of research on this, and would like to post this abstract here as a starting point. (The FISH data is interesting, but is not definitive, nor is there ONLY 1 explanation for it)

Perhaps you would like to comment on this, and then we can continue. This study was done overseas, and was "buried" so to speak amongst a mish-mosh of other data I stumbled across. A geneticist friend of mine had never seen this, and after reviewing it, pointed out the many differences also noted at the fusion point.

He made an "off the record" comment to me, that if it turns out those "differences" have specific and unique purposes in the human genome, the evidence for an ancestral "chimp" fusion would be weakened.

ABSTRACT: Similarities in chromosome banding patterns and homologies in DNA sequence between chromosomes of the great apes and humans have suggested that human chromosome 2 originated through the fusion of two ancestral ape chromosomes. A lot of work has been directed at understanding the nature and mechanism of this fusion. The recent availability of the human chromosome-1-specific alpha satellite DNA prob D2Z and the human chromosome-2p-specific subtelomeric DNA prob D2S445 promoted us to attempt cross-hybridization with chromosomes of the chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla) and orangutan (Pongo pygmaeus)to search for equivalent locations in the great apes and to comment on the origin of human chromosome 2. The probes gave different results. No hybridization to the chromosome-2-specific alpha satellite DNA probe was observed on the presumed homologous great ape chromosomes using both high-stringency and low stringency post-hybridization washes, whereas the subtelomeric-DNA probe specific for chromosome 2p hybridized to telomeric sites of the short arm of chromosome 12 of all three great apes. These observations suggest an evolutionary difference in the number of alpha satellite DNA repeat units in the equivalent ape chromosomes presumably involved in the chromosome fusion. Nevertheless, complete conservation of DNA sequence of the subtelomeric repeat sequence D25445 in the ape chromosomes is demonstrated KEYWORDS: Chromosomes, Human, Pair 2 Evolution; DNA/GE; Chromosome Banding; Human; Pan troglodytes; Animal; Gorilla Record Identifier: NI003705

With that being said, the sum and substance of this study indicated in fact NO hybridization to the centromeric regions of ANY of the chromosomes of the great apes and only produced an indication to the telomeric region of ONE of the great ape chromosomes, namely the short-arm of chromosome 12.

So, at least the results of this study, offer little support to the idea of an ancestral fusion of 2 "chimp" chromosomes as the basis of human chromosome 2.

Existing similarities in the telomeric regions of all closely related species could certainly account for the hybridization to teleomeric regions of the great ape chromosome 12.

My apologies for taking so long to comment; I have been very busy as of late.

After reading through the article you suggested (Samonte et al.), a few things came to mind.

First, on a very cursory look at the article it would seem that their results are in direct opposition to the results of the article I referenced. My article was published two years later, and while that certainly does not mean it's results are more reliable, FISH techniques had become more accurate in 2000 than they had in 1998.

However, if you read the paper in detail, there is one fact that would suggest their findings are not so contradictory after all. In Samonte's article, in the Results and Discussion section, I noticed they wrote: "High-stringency washing conditions (0.25x SSPE) revealed no chromosomes showing centromeric signals corresponding to the chromosome-2-specific alpha satellite DNA probe (figure 1A).Employment of a low-stringency wash (2.0x SSPE)resulted in hybridization signals in nonhomologous chromosomesof all three great ape species". To me, this suggests that the high stringency washes washed any hybridized probe away to undetectable levels. Once they tried a low stringency wash, they found signals in all three species (though I am curious as to why they did not inculde this as a figure). Low stringency washes showed that the probe designed to hybridize to the centromere of human chromosome 2 (DZ2) did hybridize to nonhomologous chromosomes in the great apes - exactly what one would expect given a chromosomal fusion and common descent.

I think you've taken a leap of logic here that is simply errant. Your comment:

Low stringency washes showed that the probe designed to hybridize to the centromere of human chromosome 2 (DZ2) did hybridize to nonhomologous chromosomes in the great apes - exactly what one would expect given a chromosomal fusion and common descent.

I think you are missing so much here, it's difficult to know exactly where to begin. In a sense you answered your own question, but perhaps just didn't like it?

"Once they tried a low stringency wash, they found signals in all three species (though I am curious as to why they did not inculde this as a figure)."

Procedurally you are working backwards. The normal course is to BEGIN with a low-stringency wash, NOT work your way down.

The second point (key) is the term "Non-homologous" which of course indicates much. So, even under your scenario the match was non specific, or better put there was still no match in the homologous chromosomes which is certainly what you are looking for in trying to tie this little package together. Unfortunately it doesn't work.

It is rather apparent the author's didn't include it, because it was simply "noise."

Your further leap in stating:

"...exactly what one would expect given a chromosomal fusion and common descent."

is not supported by the evidence.

I also noticed you made no mention of the telomere matches, which on surface would help your case. Whether you simply missed it, or didn't comment for another reason is not apparent to me.

In any event, it may have been propitious, as telomeric "matches" are quite easy to come by.

I will include here an abstract which shows a Telomeric repeat from a ciliated protozoan that cross hybridizes with human telomeres.

AbstractThe ends (telomeres) of eukaryotic chromosomes must have special features to ensure their stability and complete replication. Studies in yeast1–3, protozoa4–6, slime moulds7,8 and flagellates8,10 show that telomeres are tandem repeats of simple sequences that have a G-rich and a C-rich strand. Mammalian telomeres have yet to be isolated and characterized, although a DNA fragment within 20 kilobases of the telomeres of the short arms of the human sex chromosomes has been isolated11. Recently we showed that a chromosome from the fission yeast Schizosaccharomyces pombe could, in some cases, replicate as an autonomous mini-chromosome in mouse cells12. By extrapolation from other systems1,3,13,14, we reasoned that mouse telomeres could be added to the S. pombe chromosome ends in the mouse cells. On setting out to test this hypothesis we found to our surprise that the telomeric probe used (containing both the S. pombe and Tetrahymena thermophila repeats) hybridized to a series of discrete fragments in normal mouse DNA and DNA from a wide range of eukaryotes. We show here that the sequences hybridizing to this probe are located at the telomeres of most, if not all, human chromosomes and are similar to the Tetrahymena telomeric-repeat component of the probe.

So, unless you want to argue that this is evidence that the chromosomes of the protozoa and homo sapien sapiens come from the same source, perhaps it was good for your case that you didn't address it.